tbuckley/cabot-search huggingface dataset:
Prevalence of Adverse Childhood Experiences Among U.S. Adults — Behavioral Risk Factor Surveillance System, 2011–2020
Authors: Elizabeth A. Swedo, Maria V. Aslam, Linda L. Dahlberg, Phyllis Holditch Niolon, Angie S. Guinn, Thomas R. Simon, James A. Mercy
Journal: MMWR Morbidity and Mortality Weekly Report (2023)

Adverse childhood experiences (ACEs) are defined as preventable, potentially traumatic events that occur among persons aged <18 years and are associated with numerous negative outcomes; data from 25 states indicate that ACEs are common among U.S. adults (1). Disparities in ACEs are often attributable to social and economic environments in which some families live (2,3). Understanding the prevalence of ACEs, stratified by sociodemographic characteristics, is essential to addressing and preventing ACEs and eliminating disparities, but population-level ACEs data collection has been sporadic (1). Using 2011-2020 Behavioral Risk Factor Surveillance System (BRFSS) data, CDC provides estimates of ACEs prevalence among U.S. adults in all 50 states and the District of Columbia, and by key sociodemographic characteristics. Overall, 63.9% of U.S. adults reported at least one ACE; 17.3% reported four or more ACEs. Experiencing four or more ACEs was most common among females (19.2%), adults aged 25-34 years (25.2%), non-Hispanic American Indian or Alaska Native (AI/AN) adults (32.4%), non-Hispanic multiracial adults (31.5%), adults with less than a high school education (20.5%), and those who were unemployed (25.8%) or unable to work (28.8%). Prevalence of experiencing four or more ACEs varied substantially across jurisdictions, from 11.9% (New Jersey) to 22.7% (Oregon). Patterns in prevalence of individual and total number of ACEs varied by jurisdiction and sociodemographic characteristics, reinforcing the importance of jurisdiction and local collection of ACEs data to guide targeted prevention and decrease inequities. CDC has released prevention resources, including Preventing Adverse Childhood Experiences: Leveraging the Best Available Evidence, to help provide jurisdictions and communities with the best available strategies to prevent violence and other ACEs, including guidance on how to implement those strategies for maximum impact (4-6).
Type 2 Diabetes and Its Association With Psychiatric Disorders in Young Adults in South Korea
Authors: Min-Kyung Lee, Su-Young Lee, Seo-Young Sohn, Jiyeon Ahn, Kyungdo Han, Jae-Hyuk Lee
Journal: JAMA Network Open (2023)

Importance Because type 2 diabetes (T2D) has become increasingly prevalent among young adults, the study of the association of T2D with psychiatric disorders in young adults is important for early detection and timely intervention. Objective To determine whether a diagnosis of a psychiatric disorder is associated with increased risk of developing T2D in young adults. Design, Setting, and Participants This large-scale prospective cohort study used data collected by the South Korean National Health Insurance Service between 2009 and 2012, representing 97% of the South Korean population. Young adults aged 20 to 39 years with and without diagnoses of psychiatric disorders were included in the study. Young adults with missing data and those with a history of T2D were excluded from the study. The cohort was followed up to monitor development of T2D until December 2018. Data were analyzed from March 2021 to February 2022. Exposure Diagnosis of 1 of 5 psychiatric disorders, including schizophrenia, bipolar disorder, depressive disorder, anxiety disorder, and sleep disorder. Main Outcomes and Measures The primary outcome was newly diagnosed T2D during a follow-up period of 7.59 years. The incidence rate of T2D was calculated as the number of new cases per 1000 person-years during the follow-up period. The Cox proportional hazards regression model was used to estimate the hazard ratios (HRs) and 95% CIs for T2D incidence. Exploratory analyses were performed for subgroups stratified by age and sex. Results In total, 6 457 991 young adults (mean [SD] age, 30.74 [4.98] years; 3 821 858 men [59.18%]) were followed up, including 658 430 individuals with psychiatric disorders. The cumulative incidence of T2D differed significantly between individuals with and without psychiatric disorders (log-rank test, P &amp;amp;lt; .001). Incidence rates of T2D for individuals with and without psychiatric disorders were 2.89 and 2.56 per 1000 person-years, respectively. Individuals with a diagnosis of any psychiatric disorder showed a higher risk of developing T2D than those without a diagnosis (adjusted HR, 1.20; 95% CI, 1.17-1.22). The adjusted HRs for T2D were 2.04 (95% CI, 1.83-2.28) for individuals with schizophrenia, 1.91 (95% CI, 1.73-2.12) for individuals with bipolar disorder, 1.24 (95% CI, 1.20-1.28) for individuals with depressive disorder, 1.13 (95% CI, 1.11-1.16) for individuals with anxiety disorder, and 1.31 (95% CI, 1.27-1.35) for individuals with sleep disorder. Conclusions and Relevance In this large-scale prospective cohort study of young adults, 5 psychiatric disorders were significantly associated with an increased risk of developing T2D. Young adults with schizophrenia and bipolar disorder in particular were at a higher risk of T2D. These results have important implications for early detection of and timely intervention in T2D for young adults with psychiatric disorders.
Genetic associations with parental investment from conception to wealth inheritance in six cohorts
Authors: Jasmin Wertz, Terrie E. Moffitt, Louise Arseneault, J. C. Barnes, Michel Boivin, David L. Corcoran, Andrea Danese, Robert J. Hancox, HonaLee Harrington, Renate M. Houts, Stephanie Langevin, Hexuan Liu, Richie Poulton, Karen Sugden, Peter T. Tanksley, Benjamin S. Williams, Avshalom Caspi
Journal: Nature Human Behaviour (2023)

Genetic inheritance is not the only way parents' genes may affect children. It is also possible that parents' genes are associated with investments into children's development. We examined evidence for links between parental genetics and parental investments, from the prenatal period through to adulthood, using data from six population-based cohorts in the UK, US and New Zealand, together totalling 36,566 parents. Our findings revealed associations between parental genetics-summarized in a genome-wide polygenic score-and parental behaviour across development, from smoking in pregnancy, breastfeeding in infancy, parenting in childhood and adolescence, to leaving a wealth inheritance to adult children. Effect sizes tended to be small at any given time point, ranging from RR = 1.12 (95% confidence interval (95%CI) 1.09, 1.15) to RR = 0.76 (95%CI 0.72, 0.80) during the prenatal period and infancy; β = 0.07 (95%CI 0.04, 0.11) to β = 0.29 (95%CI 0.27, 0.32) in childhood and adolescence, and RR = 1.04 (95%CI 1.01, 1.06) to RR = 1.11 (95%CI 1.07, 1.15) in adulthood. There was evidence for accumulating effects across development, ranging from β = 0.15 (95%CI 0.11, 0.18) to β = 0.23 (95%CI 0.16, 0.29) depending on cohort. Our findings are consistent with the interpretation that parents pass on advantages to offspring not only via direct genetic transmission or purely environmental paths, but also via genetic associations with parental investment from conception to wealth inheritance.
Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci
Authors: Xikun Han, Puya Gharahkhani, Andrew R. Hamel, Jue Sheng Ong, Miguel E. Rentería, Puja Mehta, Xianjun Dong, Francesca Pasutto, Christopher Hammond, Terri L. Young, Pirro Hysi, Andrew J. Lotery, Eric Jorgenson, Hélène Choquet, Michael Hauser, Jessica N. Cooke Bailey, Toru Nakazawa, Masato Akiyama, Yukihiro Shiga, Zachary L. Fuller, Xin Wang, Alex W. Hewitt, Jamie E. Craig, Louis R. Pasquale, David A. Mackey, Janey L. Wiggs, Anthony P. Khawaja, Ayellet V. Segrè, Stuart MacGregor
Journal: Nature Genetics (2023)

Abstract Glaucoma, a leading cause of irreversible blindness, is a highly heritable human disease. Previous genome-wide association studies have identified over 100 loci for the most common form, primary open-angle glaucoma. Two key glaucoma-associated traits also show high heritability: intraocular pressure and optic nerve head excavation damage quantified as the vertical cup-to-disc ratio. Here, since much of glaucoma heritability remains unexplained, we conducted a large-scale multitrait genome-wide association study in participants of European ancestry combining primary open-angle glaucoma and its two associated traits (total sample size over 600,000) to substantially improve genetic discovery power (263 loci). We further increased our power by then employing a multiancestry approach, which increased the number of independent risk loci to 312, with the vast majority replicating in a large independent cohort from 23andMe, Inc. (total sample size over 2.8 million; 296 loci replicated at P &lt; 0.05, 240 after Bonferroni correction). Leveraging multiomics datasets, we identified many potential druggable genes, including neuro-protection targets likely to act via the optic nerve, a key advance for glaucoma because all existing drugs only target intraocular pressure. We further used Mendelian randomization and genetic correlation-based approaches to identify novel links to other complex traits, including immune-related diseases such as multiple sclerosis and systemic lupus erythematosus.
MEK1/2 regulate normal BCR and ABL1 tumor-suppressor functions to dictate ATO response in TKI-resistant Ph+ leukemia
Authors: Laura Mazzera, Manuela Abeltino, Guerino Lombardi, Anna Maria Cantoni, Stefano Jottini, Attilio Corradi, Micaela Ricca, Elena Rossetti, Federico Armando, Angelo Peli, Anna Ferrari, Giovanni Martinelli, Maria Teresa Scupoli, Carlo Visco, Massimiliano Bonifacio, Alessia Ripamonti, Carlo Gambacorti-Passerini, Antonio Bonati, Roberto Perris, Paolo Lunghi
Journal: Leukemia (2023)

Abstract Resistance to tyrosine kinase inhibitors (TKIs) remains a clinical challenge in Ph-positive variants of chronic myeloid leukemia. We provide mechanistic insights into a previously undisclosed MEK1/2/BCR::ABL1/BCR/ABL1-driven signaling loop that may determine the efficacy of arsenic trioxide (ATO) in TKI-resistant leukemic patients. We find that activated MEK1/2 assemble into a pentameric complex with BCR::ABL1, BCR and ABL1 to induce phosphorylation of BCR and BCR::ABL1 at Tyr360 and Tyr177, and ABL1, at Thr735 and Tyr412 residues thus provoking loss of BCR’s tumor-suppression functions, enhanced oncogenic activity of BCR::ABL1, cytoplasmic retention of ABL1 and consequently drug resistance. Coherently, pharmacological blockade of MEK1/2 induces dissociation of the pentameric MEK1/2/BCR::ABL1/BCR/ABL1 complex and causes a concurrent BCR Y360/Y177 , BCR::ABL1 Y360/Y177 and cytoplasmic ABL1 Y412/T735 dephosphorylation thereby provoking the rescue of the BCR’s anti-oncogenic activities, nuclear accumulation of ABL1 with tumor-suppressive functions and consequently, growth inhibition of the leukemic cells and an ATO sensitization via BCR-MYC and ABL1-p73 signaling axes activation. Additionally, the allosteric activation of nuclear ABL1 was consistently found to enhance the anti-leukemic effects of the MEK1/2 inhibitor Mirdametinib, which when combined with ATO, significantly prolonged the survival of mice bearing BCR::ABL1-T315I-induced leukemia. These findings highlight the therapeutic potential of MEK1/2-inhibitors/ATO combination for the treatment of TKI-resistant leukemia.
Evaluation of Birth Weight and Neurodevelopmental Conditions Among Monozygotic and Dizygotic Twins
Authors: Johan Isaksson, Vladislav Ruchkin, Therese Ljungström, Sven Bölte
Journal: JAMA Network Open (2023)

Importance Low birth weight is associated with an increased likelihood of neurodivergence and neurodevelopmental conditions (NDCs) such as autism, attention-deficit/hyperactivity disorder (ADHD), and intellectual disability. However, it is unclear whether birth weight contributes independently to NDCs or whether the association is predominantly driven by genetic predisposition. Objective To estimate the associations between birth weight and dimensional (trait) and categorical (diagnoses) NDC outcomes, while adjusting for genetic risks. Design, Setting, and Participants A co-twin design was applied to this case-control study conducted in Sweden. Diagnostic assessments were conducted between August 2011 and March 2022, within the Roots of Autism and ADHD Twin Study in Sweden (RATSS) during a 2.5-day participant visit to the clinic. The RATSS sample comprised phenotyped monozygotic and dizygotic twins enriched for NDCs. Data analysis was conducted in November 2022. Exposure Birth weight. Main Outcomes and Measures Categorical and dimensional operationalizations of autism, ADHD, and intellectual disability were assessed. Generalized estimating equation models were fitted across and within twin pairs. Results The study sample included 393 twins: 230 were monozygotic and 159 were dizygotic (zygosity was unknown for 4). Their median age was 15 (range, 8-37) years. There were 185 female participants (47.1%) and 208 male participants (52.9%). Across twin pairs, higher birth weight was associated with fewer autistic traits (unstandardized β [B], −5.51 [95% CI, −10.09 to −0.94]) and lower odds of autism diagnosis (OR, 0.63 [95% CI, 0.45 to 0.88]) and intellectual disability (OR, 0.42 [95% CI, 0.19 to 0.92]). Within pairs, the association between birth weight and dimensional autism (B, −17.35 [95% CI, −28.66 to −6.04]) and categorical autism (OR, 0.02 [95% CI, 0.001 to 0.42]) remained among monozygotic pairs but not dizygotic pairs. In addition, higher birth weight was associated with lower odds of ADHD diagnosis (OR, 0.003 [95% CI, 0 to 0.70]), fewer ADHD traits (B, −0.25 [95% CI, −0.39 to −0.11]), and higher IQ ratings (B, 7.43 [95% CI, 1.05 to 13.82]) among monozygotic twins. Conclusions and Relevance The findings of this co-twin study suggest an association between low birth weight and NDCs, but they also acknowledge the importance of genetics because the associations observed were only statically significant among monozygotic twins. It is of pivotal importance to facilitate early identification of factors contributing to fetal growth restriction to minimize detrimental outcomes.
Let Us Play the Blues: The Use of Methylene Blue for Interventional Radiology Localization of Source of Hemoptysis under Bronchoscopic Guidance
Authors: Prince Ntiamoah, Christopher Yurosko, Ihab Haddadin, Thomas R. Gildea
Journal: American Journal of Respiratory and Critical Care Medicine (2023)

"Let Us Play the Blues: The Use of Methylene Blue for Interventional Radiology Localization of Source of Hemoptysis under Bronchoscopic Guidance." American Journal of Respiratory and Critical Care Medicine, 208(8), pp. e37–e38
A novel tool for case selection in endoscopic mucosal resection training
Authors: Timothy O’Sullivan, Mayenaaz Sidhu, Sunil Gupta, Karen Byth, James Elhindi, David Tate, Oliver Cronin, Anthony Whitfield, Hunter Wang, Eric Lee, Stephen Williams, Nicholas G. Burgess, Michael J. Bourke
Journal: Endoscopy (2023)

Background As endoscopic mucosal resection (EMR) of large (≥ 20 mm) adenomatous nonpedunculated colonic polyps (LNPCPs) becomes widely practiced outside expert centers, appropriate training is necessary to avoid failed resection and inappropriate surgical referral. No EMR-specific tool guides case selection for endoscopists learning EMR. This study aimed to develop an EMR case selection score (EMR-CSS) to identify potentially challenging lesions for “EMR-naïve” endoscopists developing competency. Methods Consecutive EMRs were recruited from a single center over 130 months. Lesion characteristics, intraprocedural data, and adverse events were recorded. Challenging lesions with intraprocedural bleeding (IPB), intraprocedural perforation (IPP), or unsuccessful resection were identified and predictive variables identified. Significant variables were used to form a numerical score and receiver operating characteristic curves were used to generate cutoff values. Results Of 1993 LNPCPs, 286 (14.4 %) were in challenging locations (anorectal junction, ileocecal valve, or appendiceal orifice), 368 (18.5 %) procedures were complicated by IPB and 77 (3.9 %) by IPP; 110 (5.5 %) procedures were unsuccessful. The composite end point of IPB, IPP, or unsuccessful EMR was present in 526 cases (26.4 %). Lesion size, challenging location, and sessile morphology were predictive of the composite outcome. A six-point score was generated with a cutoff value of 2 demonstrating 81 % sensitivity across the training and validation cohorts. Conclusions The EMR-CSS is a novel case selection tool for conventional EMR training, which identifies a subset of adenomatous LNPCPs that can be successfully and safely attempted in early EMR training.
Embryonic stem cell-derived extracellular vesicles rejuvenate senescent cells and antagonize aging in mice
Authors: Lu Yu, Hang Wen, Chang Liu, Chen Wang, Huaxin Yu, Kaiyue Zhang, Qingsheng Han, Yue Liu, Zhongchao Han, Zongjin Li, Na Liu
Journal: Bioactive Materials (2023)

Aging is a degenerative process that leads to tissue dysfunction and death. Embryonic stem cells (ESCs) have great therapeutic potential for age-related diseases due to their capacity for self-renewal and plasticity. However, the use of ESCs in clinical treatment is limited by immune rejection, tumourigenicity and ethical issues. ESC-derived extracellular vesicles (EVs) may provide therapeutic effects that are comparable to those of ESCs while avoiding unwanted effects. Here, we fully evaluate the role of ESC-EVs in rejuvenation in vitro and in vivo. Using RNA sequencing (RNA-Seq) and microRNA sequencing (miRNA-Seq) screening, we found that miR-15b-5p and miR-290a-5p were highly enriched in ESC-EVs, and induced rejuvenation by silencing the Ccn2-mediated AKT/mTOR pathway. These results demonstrate that miR-15b-5p and miR-290a-5p function as potent activators of rejuvenation mediated by ESC-EVs. The rejuvenating effect of ESC-EVs was further investigated in vivo by injection into aged mice. The results showed that ESC-EVs successfully ameliorated the pathological age-related phenotypes and rescued the transcriptome profile of aged mice. Our findings demonstrate that ESC-EVs treatment can rejuvenate senescence both in vitro and in vivo and suggest the therapeutic potential of ESC-EVs as a novel cell-free alternative to ESCs for age-related diseases.
Infusible Extracellular Matrix Biomaterial Promotes Vascular Integrity and Modulates the Inflammatory Response in Acute Traumatic Brain Injury
Authors: Miranda D. Diaz, Rebecca M. Kandell, Jason R. Wu, Alexander Chen, Karen L. Christman, Ester J. Kwon
Journal: Advanced Healthcare Materials (2023)

Traumatic brain injury (TBI) affects millions of people each year and, in many cases, results in long-term disabilities. Once a TBI has occurred, there is a significant breakdown of the blood-brain barrier resulting in increased vascular permeability and progression of the injury. In this study, the use of an infusible extracellular matrix-derived biomaterial (iECM) for its ability to reduce vascular permeability and modulate gene expression in the injured brain is investigated. First, the pharmacokinetics of iECM administration in a mouse model of TBI is characterized, and the robust accumulation of iECM at the site of injury is demonstrated. Next, it is shown that iECM administration after injury can reduce the extravasation of molecules into the brain, and in vitro, iECM increases trans-endothelial electrical resistance across a monolayer of TNFα-stimulated endothelial cells. In gene expression analysis of brain tissue, iECM induces changes that are indicative of downregulation of the proinflammatory response 1-day post-injury/treatment and neuroprotection at 5 days post-injury/treatment. Therefore, iECM shows potential as a treatment for TBI.
Predicting Functional Recovery and Quality of Life in Older Patients Undergoing Colorectal Cancer Surgery: Real-World Data From the International GOSAFE Study
Authors: Isacco Montroni, Giampaolo Ugolini, Nicole M. Saur, Siri Rostoft, Antonino Spinelli, Barbara L. Van Leeuwen, Nicola De Liguori Carino, Federico Ghignone, Michael T. Jaklitsch, Jakub Kenig, Anna Garutti, Chiara Zingaretti, Flavia Foca, Bernadette Vertogen, Oriana Nanni, Steven D. Wexner, Riccardo A. Audisio, Giovanni Taffurelli, Davide Zattoni, Paola Tramelli, Giacomo Sermonesi, Giorgio Ercolani, Francesca Tauceri, Barbara Perenze, Daniela Di Pietrantonio, Mariateresa Mirarchi, Gianluca Garulli, Vincenzo Alagna, Andrea Lucchi, Basilio Pirrera, Francesco Monari, Luigi Conti, Patrizio Capelli, Andrea Romboli, Gerardo Palmieri, Filippo Banchini, Francesca Di Candido, Michele Carvello, Matteo Sacchi, Francesca De Lucia, Caterina Foppa, Luigi Marano, Alessandro Spaziani, Giampaolo Castagnoli, Alberto Bartoli, Laura Frain, Sam W. Fox, Kristin Cardin, Luis E. De Leon, Mario Trompetto, Gaetano Gallo, Alberto Realis Luc, Giuseppe Clerico, Giuseppe Sammarco, Raffaele De Luca, Michele Simone, Anna Albano, Michael Fejka, Joshua IS Bleier, Matthijs Plas, Hanneke van der Wal-Huisman, Andrea Costanzi, Giulio Mari, Dario Maggioni, Roberta Pellegrino, Valentina Riggio, Jakub Kenig, Kinga Szabat, Stefano Scabini, Davide Pertile, Lorenzo Epis, Andrea Massobrio, Domenico Soriero, Arild Nesbakken, Ingeborg Flåten Backe, Mariann Lønn, Giovanni Ferrari, Michele Mazzola, Carmelo Magistro, Pietro Achilli, Alessandro Giani, Orestis Ioannidis, Lydia Loutzidou, Konstantinos Galanos-Demiris, Gianluca Pellino, Genoveffa Balducci, Barbara Frezza, Alessio Lucarini, Claudia Santos, Lisa Cooper, Baha Siam, Yochai Levy, Baruch Brenner, Hanoch Kashtan, Valerio Belgrano, Franco Decian, Beatrice Palermo, Roberto Eggenhöffner, Manuela Albertelli, Luis Sánchez-Guillén, Antonio Arroyo, Francisco López-Rodríguez, Sandra Lario, Cristina Lillo, Minas Baltatzis, Anthony K.C. Chan, Ajith K. Siriwardena, Giovanna Da Silva
Journal: Journal of Clinical Oncology (2023)

The GOSAFE study evaluates risk factors for failing to achieve good quality of life (QoL) and functional recovery (FR) in older patients undergoing surgery for colon and rectal cancer.
Improving Report of the ADAURA Trial by Distinguishing Treatment-Related Adverse Events From Treatment-Emergent Adverse Events and Assessing Independence of Censoring in Final Disease-Free Survival Analyses
Authors: Danna Wu, Guo-Fu Li
Journal: Journal of Clinical Oncology (2023)

Herbst et al 1 present the final disease-free survival (DFS) analysis of the phase III ADAURA (ClinicalTrials.govidentifier: NCT02511106) trial which shows a meaningful DFS benefit with adjuvant osimertinib over placebo in epidermal growth factor receptor-mutated stage IB-IIIA non-small-cell lung cancer (NSCLC) after complete tumor resection (hazard ratio [HR], 0.27 [95% CI, 0.21 to 0.31]).The authors also report the long-term profile of safety with osimertinib versus placebo.Although the final data of DFS and adverse events are important, we believe that there are few crucial concerns that necessitate further explorations.